Expression of angiotensin-converting enzyme-2 (ACE2) in experimental diabetic retinopathy and influence on it of cellular protein kinases blockade
DOI:
https://doi.org/10.14739/2310-1237.2025.2.329800Keywords:
diabetic retinopathy, angiotensin-converting enzyme 2, sorafenibAbstract
Disruption of the renin-angiotensin system (RAS) of the eye is a causal factor in diabetic microvascular complications. The effects of RAS are counteracted by a recently discovered axis involving angiotensin-converting enzyme type 2 (ACE2) and its product angiotensin 1-7.
Aim: to determine the expression and content of ACE2 in the retina in experimental diabetic retinopathy (DR) and to establish the effect of blockade of cellular protein kinases on them.
Materials and methods. DR was modeled in male Wistar rats. For this purpose, they were administered streptozotocin once at a dose of 50 mg/kg (Sigma-Aldrich, Co, China). Experimental rats were divided into four groups: control; with the administration of insulin 30 U (NovoNordiskA/S, Bagsvaerd, Germany); with the administration of the protein kinase inhibitor sorafenib (Cipla, India) at a dose of 50 mg/kg; with the administration of insulin and sorafenib. During immunoblotting and immunohistochemical studies, monoclonal antibodies against ACE2 (EMD Millipore Corporation, USA) were used.
Results. A multiple increase in the content of ACE2 in the diabetic retina was established, first the accumulation of its free isoforms, and then binding to cellular proteins. Also, during the observation, an increase in the expression of ACE2 in the vessel walls was noted, which confirmed the involvement of this important RAS regulator in the pathogenesis of diabetic retinal damage. Insulin administration reduced the content of ACE2 after 21 days and 2 months of treatment to a greater extent than its combined administration with sorafenib, or separate administration of sorafenib. After 3 months, the content of ACE2, especially its high-molecular forms, was more effectively reduced by the combined administration of insulin with sorafenib than by separate administration of insulin.
Conclusion. The results obtained showed a possible role of increased ACE2 expression in the pathogenesis of DR and revealed its decrease during treatment with insulin and sorafenib, which corresponded to the inhibition of the development of morphological signs of DR.
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Copyright (c) 2025 K. O. Usenko, S. O. Rykov, O. O. Dyadyk, A. O. Tykhomyrov, S. V. Ziablitsev
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